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SIV Latency in Macrophages in the CNS.

Authors
  • Gama, Lucio1
  • Abreu, Celina1
  • Shirk, Erin N1
  • Queen, Suzanne E1
  • Beck, Sarah E1
  • Metcalf Pate, Kelly A1
  • Bullock, Brandon T1
  • Zink, M Christine1
  • Mankowski, Joseph L1, 2, 3
  • Clements, Janice E4, 5, 6
  • 1 Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • 2 Department of Neurology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • 3 Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • 4 Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA. [email protected]
  • 5 Department of Neurology, Johns Hopkins University, Baltimore, MD, 21205, USA. [email protected]
  • 6 Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA. [email protected]
Type
Published Article
Journal
Current topics in microbiology and immunology
Publication Date
May 17, 2018
Identifiers
DOI: 10.1007/82_2018_89
PMID: 29770863
Source
Medline
License
Unknown

Abstract

Lentiviruses infect myeloid cells, leading to acute infection followed by persistent/latent infections not cleared by the host immune system. HIV and SIV are lentiviruses that infect CD4+ lymphocytes in addition to myeloid cells in blood and tissues. HIV infection of myeloid cells in brain, lung, and heart causes tissue-specific diseases that are mostly observed during severe immunosuppression, when the number of circulating CD4+ T cells declines to exceeding low levels. Antiretroviral therapy (ART) controls viral replication but does not successfully eliminate latent virus, which leads to viral rebound once ART is interrupted. HIV latency in CD4+ lymphocytes is the main focus of research and concern when HIV eradication efforts are considered. However, myeloid cells in tissues are long-lived and have not been routinely examined as a potential reservoir. Based on a quantitative viral outgrowth assay (QVOA) designed to evaluate latently infected CD4+ lymphocytes, a similar protocol was developed for the assessment of latently infected myeloid cells in blood and tissues. Using an SIV ART model, it was demonstrated that myeloid cells in blood and brain harbor latent SIV that can be reactivated and produce infectious virus in vitro, demonstrating that myeloid cells have the potential to be an additional latent reservoir of HIV that should be considered during HIV eradication strategies.

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